P705: MULTI-CENTER CHART REVIEW STUDY EXAMINING TREATMENT PATTERNS AND CLINICAL OUTCOMES AMONG PATIENTS WITH CHRONIC PHASE (CP) CHRONIC MYELOID LEUKEMIA (CML) TREATED IN THIRD-LINE (3L) OR LATER IN FRANCE
Authors: F. E. Nicolini, G. Etienne, F. Huguet, M. Gu, C. Bouvier, A. Yocolly, R. Favier, M. Trancart, L. Huynh
Journal: HemaSphere (2022)

Background: The standard of care for CML has substantially evolved over a relatively short period of time; pharmacologic inhibition of ABL1 with adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitors (TKIs) remains the cornerstone of modern treatment. Clinical guidelines for CP-CML recommend that patients who have failed ≥2 prior TKIs switch to an alternative 2nd or 3rd generation TKI. However, up to 65% of these patients have prior exposure to ATP-competitive TKIs and history of either TKI intolerance or resistance. Aims: This retrospective, multi-center, chart review study aimed to characterize the disease burden, treatment patterns, and clinical outcomes of CP-CML patients who have failed ≥2 TKIs. Methods: De-identified demographic and clinical data for adult patients diagnosed with CP-CML treated in 3L or later at three reference centers in France were abstracted from medical charts using electronic case report forms. Descriptive statistics were summarized for patient characteristics, clinical outcomes during 3L treatment, and adverse events. Molecular data were standardized and expressed in the international scale (IS). The cumulative incidence of patients achieving molecular response (major molecular response [MMR, 0.01% IS ≤0.1%] or deep molecular response [MR4.0, 0.0032% < BCR–ABL1IS ≤0.01% or MR4.5, BCR–ABL1IS ≤0.0032%]) were summarized at specific time points. Progression-free survival (PFS) and overall survival (OS) from 3L initiation were examined using the Kaplan–Meier (KM) method. Results: Medical data for 157 CP-CML patients were assessed; the mean follow-up was 66.9 months, the median age at 3L initiation was 62.1 years, 56% were male, and 90% had major BCR-ABL1 rearrangement (among the 89 patients with mutation status assessed, 7 [8%] had BCR-ABL1 T315I mutation, 3 [3%] had M244V, and 3 [3%] had F359I). According to EUTOS long-term survival score, 40% of patients had low risk, 25% had intermediate risk, and 11% had high risk of death due to CML. Cardiovascular diseases were present in 55% of patients at 3L; mean systolic and diastolic blood pressure were 140.9 and 78.9 mmHg, respectively. Mean ± SD low-density lipoprotein cholesterol was 141.0 ± 54.0 mg/dl. Median duration of 3L therapy was 17.0 months. TKIs received in 3L were dasatinib (32%), nilotinib (19%), imatinib (18%), ponatinib (17%), and bosutinib (14%). Treatment-free remission was initiated by 16 (10%) patients. In patients with documented responses, 42% patients achieved MMR, 27% achieved MR4.0, and 14% achieved MR4.5 at 12 months. Although median PFS and OS were not reached as of data collection, 19 (12%) patients died due to disease progression (n=7), toxicity (n=1), or other reasons (n=10) and 1 patient had an unknown cause of death. Approximately 50% of patients discontinued treatment; 37% had ≥4 lines of treatment and 16% had ≥5 lines. The primary reasons for discontinuation (not mutually exclusive) were intolerance (54/78 [69%]), resistance (18/78 [23%]), and signs of ineffectiveness (14/78 [18%]). AEs were documented for 139/157 patients (89%). The mean number of AEs per patient was 2.7; infections (18%) and asthenia (13%) were the more commonly documented AEs. Summary/Conclusion: CP-CML patients continue to experience a substantial disease burden and poor prognosis after 3L treatment with available TKIs, underscoring the need for novel therapies that are well tolerated and can achieve durable responses.